研究动态
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胚胎中胚垂体酶基质金属蛋白酶28对神经嵴上皮间质转化的旁分泌调控

Paracrine regulation of neural crest EMT by placodal MMP28.

发表日期:2023 Aug 17
作者: Nadège Gouignard, Anne Bibonne, João F Mata, Fernanda Bajanca, Bianka Berki, Elias H Barriga, Jean-Pierre Saint-Jeannet, Eric Theveneau
来源: PLOS BIOLOGY

摘要:

上皮间质转化(EMT)是细胞从上皮组织转变为间充质的早期事件。EMT赋予细胞具有迁移和有时侵袭性的能力,因此是胚胎形态发生和癌症进展的关键过程。迄今为止,基质金属蛋白酶(MMPs)尚未被认为是EMT中的关键因子,而是研究它们在后续事件(如细胞迁移本身)中的基质重塑作用。在这里,我们使用蛙类神经嵴(NC)细胞评估MMP28在体内的EMT和迁移中的作用。我们展示了紧邻的斑状细胞中表达的催化活性MMP28对NC的EMT和细胞迁移起关键作用。我们提供了有力的证据表明MMP28被导入到NC细胞的细胞核中,其对Twist表达是必需的。我们的数据表明MMP28可以作为EMT的上游调控因子在体内发挥作用,从而引发了其他MMPs在癌症、纤维化和创伤愈合等各种EMT相关环境中可能具有类似早期作用的可能性。 版权所有:© 2023 Gouignard等人。本文为自由使用文章,按照知识共享署名许可协议,允许在任何媒体上自由使用、分发和再制作,前提是原作者及出处得到了充分的认可。
Epithelial-mesenchymal transition (EMT) is an early event in cell dissemination from epithelial tissues. EMT endows cells with migratory, and sometimes invasive, capabilities and is thus a key process in embryo morphogenesis and cancer progression. So far, matrix metalloproteinases (MMPs) have not been considered as key players in EMT but rather studied for their role in matrix remodelling in later events such as cell migration per se. Here, we used Xenopus neural crest (NC) cells to assess the role of MMP28 in EMT and migration in vivo. We show that a catalytically active MMP28, expressed by neighbouring placodal cells, is required for NC EMT and cell migration. We provide strong evidence indicating that MMP28 is imported in the nucleus of NC cells where it is required for normal Twist expression. Our data demonstrate that MMP28 can act as an upstream regulator of EMT in vivo raising the possibility that other MMPs might have similar early roles in various EMT-related contexts such as cancer, fibrosis, and wound healing.Copyright: © 2023 Gouignard et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.